[!INFO] Intrinsic muscle nerve supply
All the intrinsic muscles of the hand except the lateral two lumbricals cause supplied by the ulnar nerve.
The lateral lumbricals are supplied by the median nerve.
Brachials plexus is made up of C5 to T1 nerve roots

[!TIP] Mnemonic: Klumpkey the Monkey
monkey hangs -> C8/T1 lesion

Klumpke's paralysis (KP)	Erb's palsy
C8 / T1 lesion	C5/C6
Claw hand due to unopposed action of long flexors and extensors	Shoulder adducted, elbow extended, forearem pronated (waiters tip)
Can have associated Horner's Xn (C8,T1 are in close proximity to sympathetic chain).	Also winged scapula
Damage to one can cause damage to the other.	more common than Klumpke's
Seen in breech delivery. (upward traction on arm)	Shoulder dystocia
Loss of function of lubricals and wrist flexors	Deltoid, biceps, brachialis affected.
Lumbricals flex the MCP joints and extend the PIP and DIP joints;
In KP, The wrist and the MCP are extended and the DIP and PIP are flexed.
C8 / T1 - Medial forearm sensory loss	sensory loss in lateral forearm, lateral aspect of upper arm.

Ulnar claw

Medial two lumbrical are supplied by the ulnar nerve;
Lateral two lumbricals are supplied by the median nerve.
In ulnar claw hand, the lesion is similar to klumpke's but limited to the lateral two fingers.

Causes of diabetes insipidus

Central	Nephrogenic
Intracranial SOL / pituitary surgery / trauma etc	Lithium
Infiltrative diseases: Histiocytosis, Sarcoidosis, (but ?not amy_loidosis)	⬆Ca, ⬇K
Haemochromatosis	Demecloclycline
DIDMOAD (ada Wolfram Syndrome)	Inherited: Common- ADH receptor mutation Rare: aquaporin 2 mutation

• Right side to right side. Left to left.
• fibers from superior half travel superiorly (parietal lobe) , fibers from inferior half travel inferiorly (temporal lobe)
  Lateral views showing the optic radiations:
  

[!INFO] Relevant cerebral lobes
Mnemonic: PITS ->

• Parietal lobe lesions -> inferior visual loss
• Temporal lobe lesions -> superior visual loss.

• Retrolenticular - inferior visual quadrants - In the parietal lobe
• sublenticular - superior visual quadrants - In the Temporal lobe.

Characteristic	EDH-epidural/ extradural	SDH-subdural
Patient	Young, Hx of trauma	Old
Aetiology	Usually trauma, spontaneous is very rare	Commonest is traumatic, cerebral atrophy (old age, chronic alcohol use) is a major risk factor
	-	Tamponade effect will control rate of bleeding (as it’s venous)
Type of bleed	80% arterial, therefore rapid	Mostly venous / small arteries
Site	Commonly middle meningeal artery at [[foramen spinosum.png]]	Bridging vein or other sites
Plane	Potential space between dura and skull	Between dura and arachnoid
Presentation	Lucid interval → rapid decrease	Can be acute or chronic.
Imaging	Lens shaped, does not cross suture lines, crosses dural attachments	Crescent shaped, crosses suture lines, does not cross dural attachments
	-	Chronic changes occur: Encapsulation and resorption / hygroma formation
	Also seen in trauma	most common type seen in trauma
	Lower impact, lucid interval present	Caused by Higher energy impacts - patient won't regain consciousness
	brief, linear contact force to the skull.	Can Occur in less severe trauma (antigoagulants, old age are RF)
	Arterial or venous. (commonest site = middle meningeal artery); caused by disruption of vessels secondary to dura separating from skull.	Mechanism: tearing of veins due to relative movement of brain due to acceleration
	rare in age > 60 as 'dura is tightly adherent to the skull'	highest incidence in 40s to 70s.
	most are acute.	Can be acute or chronic
Source

OR
Wernicke = Word Salad. (W - W)

• Neglect syndromes - parietal lobe involvement
  • More commonly affects right sided lesions. (commonest cause is a stroke).

[!TIP] Mnemonic: The parietal lobe is responsible for interpretation of "things in space";
Symbols lose meaning - agraphia, acalculia, alexia,
Disorientation
Spatial structure of tactile stimuli is lost - "cortical sensory loss"
Astereognosis

8. simultagnosis (inability to identify things in context - i.e can see trees but can't recognize Forrest)
9. Hemispatial neglect

Temporal lobe dysfunction

[!TIP] Mnemonic:
The temporal lobe seems to be involved in

1. processing and interpretation of sensory stimuli
2. predominantly auditory, also visual, smell etc.
3. Emotional regulation
4. Memory

Functions:

1. Processing sensory stimuli - Mainly sound ( but also vision, smell etc)
2. Memory - Hippocampus. (hippocampus is involved in making long term, emotionally connected memories)
3. Language comprehension
4. Understanding social cues
5. Facial recognition
6. Emotional regulation -> possibly due to involvement of the amygdala which is located in the medial temporal lobe.
   1. fear is a predominant emotion seen in temporal lobe problems.
7. Attention
8. Reward processing and motivation.

Features of temporal lobe dysfunction:

• Difficulty recognizing faces : prosopagnosia
• Visual agnosia - inability to identify objects.

Causes of QT prolongation:

4. Amiodarone is the drug of choice for for treatment of haemodynamically unstable VT.
5. Verapamil should never be used in VT - ?why
   F

The classic description of the left cardiac ventricle is as containing two papillary muscles: the anterolateral and posteromedial.[2] The anterolateral arises from the sternocostal wall, and the posteromedial papillary muscle arises from the diaphragmatic wall of the ventricle. The right ventricle contains three papillary muscles, classically described as anterior, posterior, and septal. Source

Left anterolateral papillary muscles derives from branches of the left coronary artery. The blood supply to the left posteromedial papillary muscles most commonly derives from the right coronary artery Source

[!INFO] Azithromycin
used as last resort add on therapy
Reduces exacerbation frequency but promotes antibiotic resistance.

Pulmonary arterial hypertension

• Pulmonary pressure ≥ 25mmHg. (UpToDate = 20mmHg)
• WHO recognized 5 groups based on aetiology
  • Group 1 - Pulmonary arterial hypertension
    • Subdivided into IPAH - idiopathic PAH
    • Heritable (HPAH)
  • Group 2 - Left heart disease
  • Group 3 - chronic lung disease / hypoxaemia
  • Group 4 - pulmonary artery obstruction
  • Gropu 5 - unknown aetiology

Pathologic findings in pulmonary arterial hypertension:

• hyperplasia and hypertrophy of all three layers of the vascular wall (intima, media, adventitia) in pulmonary arteries <50 microns (ie, localizes to the small pulmonary muscular arterioles).

Treatment:
Two groups:

• Acute vasodilator testing - positive response (the minority of patients) -> Treatment is calcium channel blockers.
• Acute vasodilator testing - negative response (the VAST majority of patients) -> Sildenafil, endothelin receptor antagonist (bosentan)
  • Endothelin is a vasocontrictor.

Disease modifying drugs in rheumatoid arthritis;
DMARDS are commonly co-prescribed;
Are there any bad combinations?
The drugs are divided into non-biologics and biologics, corticosteroids, and NSAIDS.

Usuallly RA doesn't have adverse effects on pregnancy.
TNF is central in disease pathogenesis.
Order of preference for use of drugs:

• DMARDS are started early - that's the standard of care now.
• Method of treatment is "treat to target" - disease activity is assessed using DAS28CRP or DAS28ESR scores.

Autoimmune diseases in pregnancy

Immune thrombocytopenia in pregnancy

• is a manifestation of the worsening of immune thrombocytopenia during pregnancy.
• Caused by maternal IgG reacting with maternal platelets.
• causes isolated low PLT.
• Diagnosis of exclusion.
• IgG crosses placenta but doesn't affect foetal platelets.
• management options:
  • steroids - response occurs but 1/2 will recur
  • IVIg improves platelets counts rapidly - good to raise counts before d
  • splenectomy - induces sustained relapse.
  • platelet transfusion if counts < 30k for NVD and <50k for LSCS.

Rheumatoid arthritis in pregnancy

• Doesn't directly affect the baby but lumbar and and hip involvement may make NVD difficult.
• pre-existing RA settles down.
• but new RA can develop postpartum.
• Management: first line is prednisolone

SLE in pregnancy

• Can worsen after delivery.
• can cause IUGR and other foetal complications
• congenital heart block in the baby due to maternal antibodies
• it's best if pregnancy can be delayed until 6 months of flare free period is achieved.
• Management of a flare in pregnancy
  • SLE flares are usually treated with low-dose prednisolone, IV pulse methylprednisolone, hydroxychloroquine, and/or azathioprine. High-dose prednisone and cyclophosphamide increase obstetric risks and are thus reserved for severe lupus complications.

Viral classification

[!INFO] Key terms:

• Reverse transcription -> using RNA to produce DNA.
• Retrovirus -> A RNA virus which uses reverse transcription to produce DNA which is then incorporated into host DNA

Examples:
Hepatitis B - hepadnaviridae
Hepatitis C - flaviviridae
HIV - retroviridae
EBV - herpesviridae
picornaviruses include - enterovirus, coxsackie virus, Hepatitis A
Orthomyxoviridae - influenza virus.
Retroviruses - HTLV-1 and HIV. (HIV uses viral integrase for DNA incorporation)

Antiviral drugs

Source
Antiviral drugs do no "kill" viruses; they only inhibit replication.

• Oseltamivir - selectively inhibits influenza neuraminidase; It inhibits release of viral particles from the host cell.
• Acylovir - Competitively inhibits viral DNA polymerase of HSV1 and HSV2 and Varicella Zoster virus.
  • Acyclovir is converted to the active form by viral proteins found only within infected cells. Therefore, drug has specificity of action.
• Anti HIV drugs - bind to the coreceptor and prevent HIV entry into cells.
• Anti HIV enfuvirtide binds to the HIV protein responsible for fusion of the viral envelope with the cell membrane
• Reverse transcriptase inhibitors : usually nucleoside or nucleotide analogs; they insert themselves into the replicating DNA and stop the process of reverse transcription. (i.e They work for RNA viruses or DNA viruses with reverse transcription)
  • Zidovudine, Lamivudine work against HIV and Hep B.
• Integrase inhibitors: Dolutegravira (drugs have 'tegra' in their names)
• DNA polymerase inhibitors : inhibit the viruses' intrinsically encoded DNA polymerase. Acylovir for herpes virus, ganciclovir for CMV; drugs are usually nucleoside analogs.
• Inhibition of viral protein synthesis:

Herpes simplex during pregnancy

[!INFO] Summary
New herpes is bad; worst if onset in T3.
Recurrence of herpes doesn't impose a significant risk.

• Neonatal herpes carries significant mortality risk.
• Infection of the neonate is by contact with maternal genital secretions.
• Risk of infection is highest when vaginal delivery occurs within 6 weeks of onset of the ulcer (before maternal antibodies have developed).
• If the mother develops genital herpes in T2 or earlier, start acylovir from 36 weeks onwards and plan for NVD.
• If the mother develops new onset genital herpes in T3, start acylovir and plan for LSCS.
• With recurrent genital herpes, the risk of neonatal infection even with NVD is low. NVD can be offered.

Acne rosacea

• Presents with erythema and papules + telangiectasia on the central face.
• Complications: rhinophyma, occural involvement with blepharitis, chalzion etc. is common.
• Occurs in middle ages and fair skinned people. (i.e ?Not Sri lankans)
• Management:
  • Topical ivermectin,
  • Systemic doxycycline (Contraindicated in #pregnancy)
  • brimonidine topical gel. (alpha agonist - transient relief from flushing)

Temp renal physiology

ADH stimulates V2 rectors on principal cells in the collecting duct to promote insertion of aquaporin channels.
The main cells in the collecting duct are principal cells. They

• are recetive to ADH
• Receptive to aldosterone -> increase expression of ENac Channels.

The intercalated cells are responsible for H+ secretion and chloride secretion.

Metabolic alkalosis

Source

[!INFO] Pendrin
Is a key transport protein involved in pathogenesis.

"internal potassium balance".

The transcellular shifts in K+ caused by acid base changes.
Basis: In acidosis, about half the H+ is buffered intracellularly. To maintain electroneutrality, intracellular K+ moves outwards into the ECF.

[!INFO] Hypoaldosteronism
In patients with hypoaldosteronism, for example, the mild metabolic acidosis is primarily due to the associated hyperkalemia
UpToDate

Familiar mediterranean fever

• #autosomal-Recessive
• Episodes of fever with serositis lasting 1-3 days. (pleurisy, pericarditis, arthritis)
• more common in Turkish, Armenian and Arabic descent.
• Colchichine produces quick relief.

Management of ACNE

• Acne is caused by hyperproliferation of keratinocytes in the pilocebaceous follicle resulting in obstruction.
• Within this environment, various changes result in formation of acne.
• Propioni bacterium acne is implicated in the pathogensis.
• Synthesis of testosterone in the follicle causes increased production of sebum.
  Therapeutic options:

1. Comedolytic topics medications - benzoyl peroxide, salicylic acid, and retinoids.
2. Systemic: isotretinoin and antiandgoren treatment.
   1. Antiandrogens are contraindicated in men.
   2. Isotretinoin reduces sebum production; Vitamin A derivative, contraindicated in pregnancy (even blood donation is contraindicated while on it); congenital malformations can result.
   3. Usually very effective for acne.
3. Antibiotics supposedly kill the bacteria:
   1. Topical clindamycin
   2. Oral doxycycline

Gynaecomastia

• Definition: benign hyperplasia of ductal tissue in the breast of males. Usually bilateral.

Clinical and pathological correlation

• Gynaecomastia is distinct from galactorrhea.
  • Galactorrhea is caused by the action of proloactin acting upon oestrogen primed glands.
  • Prolactin on it's own does not cause gynaecomastia.
    • Except in rare situation where prolacting suppresses GHRH causing hypogonadism.
• Gynaecomastia is a manifestation of oestrogen to androgen ratio imbalance.
• recall [[SteroidSynthesis2.png]]; oestrogen and testosterone are synthesized from a common precursor - androstenidione.
• In males, the testes produce very little estrogen; most oestrogen in the periphery is produced by peripheral aromatization by the aromatase enzyme.

Causes of gynaecomastia

• hCG producing tumours are an import cause of gynaecomastia. hCG acts like LH to increase testosterone production. hCG levels should be done in the workup.

[!TIP] mnemonic: Drugs causing gynaecomastia
Gay DISCO

1. Goserelin - Mechanism of Action Goserelin (a gonadotropin-releasing hormone [GnRH] analog) causes an initial increase in luteinizing hormone (LH) and follicle stimulating hormone (FSH), chronic administration of goserelin results in a sustained suppression of pituitary gonadotropins
2. Digoxin
3. Isoniazide
4. Spironolactone
5. Cimetidine
6. Oestrogen

Causes of hyperprolactinaemia

#2023GM-NOV/Q30

See also [[Hormone Physiology#Prolactin]]
Pathological causes

• Lactotroph adenoma
• Decreased dopaminergic inhibition
• Other hypothalaic or pituitary disorders

Drugs:

• Antipsychotics : commonest drugs causing hyperprolactinaemia (eg. Haloperidol, risperidone)
  • Newer drugs: occurs with amisulpride.
  • Does not occur with clozapine.
• SSRI's do NOT cause hyperprolactinaemia.
• Other drugs:
  • Metoclopramide (centrally acting dopamine and serotonin angatonist) and domperidone (peripherally acting dopamine antagonist) can cause hyperprolactinaemia .
    • Domperidone does not cross the blood brain barrier.
    • Methyldopa inhibits dopamine synthesis.

Staphylococcal toxic shock syndrome

• Acute (within 48 hours) development of fever, hypotension, rash and organ failure in otherwise healthy individuals.
• First noted due to an epidemic following tampon use.
• Surgery, other infections are now recognized as other risk factors.
• Therefore, it's a clinical diagnosis.
  • Positive saphylococcal cultures are not mandatory to make the diagnosis.
• Diffuse erythematous rash which will desquamate weeks later.
• Pathogenesis: Due to effects of TSST exotoxin produced by the staph.
• Management: Remove source of infection. (any foreign device in vaginal canal, surgical debridement of wound etc)
  • Start antibiotics. (Vancomycin (for MRSA cover) + carbapenem + clindamycin )
  • Clindamycin inhibits protein synthesis so is preferred because it will reduce toxin production.

Homocystinuria

A rare #autosomal-Recessive disorder which presents with

• marfanoid habitus
• Downward lens dislocation (as opposed to upward in marfans)
• Learning difficulty.
• caused by a deficiency of the enzyme cystathionine beta synthase.
• In Down's syndrome, there is excessive activity of cystathionine beta synthase.
• diagnosis: increased homocysteine levels in serum and urine
• Cyanide-nitroprusside test is positive.
• Treatment: vitamin B6 supplements.

Causes of acute visual loss

Unilateral:

• all the 'itis' conditions are painful.
• "The sensory nerves enter the eyeball mainly through the ciliary nerves and reach all ocular tissues with the exception of the lens and the retina." Source
• Innervation is particularly rich in the cornea.

Bilateral

• Only one cause of bilateral painful visual loss: keraritis from bilateral exposure (UV light, contact lens, chemical etc)
• Bilateral painless
  • Pseudomotor cerebri
  • Metabolic or toxic (methanol toxicity)
  • homonymous field loss (chiasmal or retrochiasmal)

Evaluation of gradual visual loss

[!INFO] Visual loss means loss of one or more of

• acuity
• Color vision
• visual field

Pearls

• Improvement of acuity with pin hole indicates uncorrected refractive error.
• Occular pathologies and prechiasmal optic neuropathies cause monocular vision loss.
• Amaurosis fugax also presents as transient monocular vision loss.
  • Consider AF as an omen of a stroke
• monocular vision loss is usually due to ocular or pre-chiasmal lesions.
  • Ocular pathologies (corneal, lenticular, vitreoretinal and macular) and prechiasmal optic neuropathies typically cause monocular vision loss.
• Binocular vision loss is usually due to retrochiasmal lesions.
  • In this case, assessment of visual fields can localize the lesions.
  • eg: temporal lobe Meyer's loop leions -> Superior homonymous quadrantonopia.
• most retinal causes of vision loss are painless
• Retrochiasmal lesions will cause contralateral homonymous visual field defects.

Central Vs. Peripheral vision loss:

• Poor central vision with peripheral sparing = macular involvement.
  • eg AMD
  • Manifests as distortions or paracentral scotoma.
• Constricted peripheral vision is usually caused by optic neuropathy.
  • eg: Chronic glaucoma
  • but there are also retinal causes of tunnel vision.
    • eg: retinitis pigmentosa

Speed of onset

• Vascular - rapid.
• Inflammatory - subacute (over days) (eg. optic neuritis, scleritis)
• Degenerative - gradual (cataract)

Leading causes of blindness

• Cataract
• Glaucoma
• Refractive error
• Age-related macular degeneration (AMD)
• Diabetic retinopathy

Retinal vessel occlusion

Source

Von hippel-lindau disease

#autosomalDominant
Hallmarks:
retinal and central nervous system (CNS) hemangioblastomas (blood vessel tumors), pheochromocytomas, multiple cysts in the pancreas and kidneys, and an increased risk for malignant transformation of renal cysts into renal cell carcinoma.

Source

Peutz-Jeghers syndrome

#autosomalDominant

• Characterized by gastrointestinal (GI) polyposis, mucocutaneous pigmented macules, and predisposition to certain cancers. Patients with Peutz-Jeghers syndrome are at an increased risk for developing GI cancers of the colorectal, pancreatic, and gastric systems, in addition to a wide variety of non-GI epithelial malignancies including breast, uterine, cervical, lung, ovarian, and testicular cancers.
• Commonest cancer is colorectal
• Caused by mutations in STK11 tumour suppressor gene on chromosome 19

Gastric polyps	mucocutaneous pigmentation

Pituitary adenomas

[!TIP] Summary
Small anterior pituitary tumours (<1cm) are commmon, nonfunctioning and asymptomatic.

Large pituitary tumours (>1cm) are less common and they can cause pressure effects or hormone imbalances.

• Tumours of the anterior pituitary. (only the anterior pituitary is glandular tissue)
  • microadenoma = < 10mm
  • macroadrenoma = > 10mm
  • Giant = > 40mm
• Surprisingly commong but most are asymptomatic.
• They are mostly found incidentally as they grow slowly and are asymptomatic.
  • about 1/4 of autopsies reveal presense of a pituitary microadenoma.
• They can be functioning or non functioning.
  • About 1/3 are non functioning - 80% of these arise from gonadotrope cells.
  • Of the functioning ones prolactinomas are the commonest.

In contrast to macroadenomas, pituitary function testing is generally not needed for microadenomas - Medscape

Pituitary microadenoma is usually an incidental finding on MRI head. Patients are asymptomatic unless the tumor is hormonally active.
Pituitary macroadenoma presents with mass effects and potentially hormonal deficiency or hormonal excess. Source

Heart blocks

[!TIP] Summary:
Mobitz I : OK
Mobitz II : BAD

• Mobitz I is due to fatigue of the AV node or functional suppression (drugs, vagal tone etc)
• Mobitz II is due to defect at the level of His-Purkinje system.
• Mobitz II is much more likely to cause haemodynamic compromise, severe bradycardia and progression to complete heart block.
• Mobitz II : Risk of asystole if 35% per year.
• Mobitz type II ultimately requires insertion of a permanent pacemaker.
  Source

Alpha-1 antitrypsin deficiency

• Is a protease inhibitor which protects tissues against the action of enzymes like neutrophil elastase.
• Deficiency causes emphysema.
• INheritance: #autosomal-Recessive
• Genetic variants:
  • PiMM = normal individual
  • PiMZ = heterozygous; risk of emphysema developing if patient is a smoker.
  • PiSS = 50% of normal antitrypsin levels;
  • PiZZ = 10% of antitrypsin levels; affected and develops emphysema

Management: intravenous alpha1-antitrypsin protein concentrates + smoking cessation, supportive bronchodilators etc .

Source <- Dynamic air trapping in COPD.

pontine haemorrhage

• A commoner form of ICH.
• caused mainly by hypertension and AV malformations.
• hypertension causes lipohyalinosis of the penetrating branches of thr basilar artery.Source
• has a poor prognosis.
• "classic" pontine hematoma syndrome is characterized by coma, quadriparesis, and death. Source
• Features
  • reticular system involvement -> reduced consciousness
  • motor tracts -> bilateral paralysis
  • pinpoint pupils
  • absent horizontal eye movment